The genetic basis of systemic lupus erythematosis has been pursued using the last five years of funding from this grant (AR24717-07 to -11) to help perform and evaluate a genome scan in lupus. These results considered with those of our closest competitor show 26 possible genetic linkages with 11 of these having some support for linkage from both studies. In addition, we confirm evidence supporting the presence of linkage at D1s229. Other work has advanced Epstein-Barr virus as a possible etiologic agent in lupus. Data show association, are consistent with Epstein-Barr virus infection preceding lupus onset, and advance a plausible mechanism for lupus autoimmunity in some patients. Virus exposure data and differences between the anti-viral immune responses of lupus patients and normal are amenable to genetic analysis in our pedigrees. In aggregate, we have 2109 pedigrees multiplex for lupus containing 1227 subjects (275 affecteds & 752 unaffecteds). We hope to continue our work by pursuing the following specific aims: 1. Enlarge the pedigree collection; 2. Establish linkage using: A. Lupus (by revised ACR criteria), B. An environmental factor and intermediate phenotypes: i. Lupus and Epstein-Barr virus infection, ii. Anti-peptide antibodies against Epstein-Barr virus (& against lupus autoantigens), iii. Anti-Ro and anti-nRNP autoantibody responses, and C. Multi-locus effects, and 3. Reduce linkage intervals and evaluate candidate genes. Hopefully, results from this resubmitted project will help elucidate the complex genetics of lupus.